The low molecular weight complement component, C5a, generated by activation of either the alternate or classical pathways, interacts with human polymorphonuclear leukocytes, in the absence of particles, to cause the selective release of lysosomal constituents. The goal of the applicant is to elucidate the factors which regulate this phenomenon, and which may be important in the pathogenesis of certain forms of immune tissue injury. The applicant's previous studies of C5a-mediated lysosomal enzyme release from cytochalasin B-treated human leukocytes will be expanded in an attempt to determine the roles played by cyclic nucleotides, microtubules, membrane fusion, energy metabolism, and divalent cations in the enzyme release process. The proposed studies will test the hypothesis that the usual shuttle and flow of lysosomes, and the recompartmentalization of their contents, may be regulated by a discrete series of events involving: a) perturbation of the plasma membrane; b) accumulation of either cAMP or cGMP: these either regulate the traffic of lysosomes or affect membranes directly; c) assembly or disassembly of cytoplasmic microtubules, and, finally; d) the fusion of lysosomal membranes with phagocytic vacuoles and/or the plasma membrane. Specific attention will be focused on the role of calcium in facilitating or initiating these events, and on the recently observed phenomenon of lysozyme secretion from human PMN's that can be provoked by calcium, in the absence of other stimuli.